Project proposes in vivo functional and structural neuroimaging, neurobehavioral studies, and postmortem histologic studies of schizophrenic patients designed to delineate the neural substrate of disturbed frontal lobe function in schizophrenia. We will focus on problems of spatial cognition and volition using oculomotor tasks for which the neurophysiologic substrates in dorsolateral prefrontal cortex (DLPFC) have been well-characterized by unit recording studies in non- human primates. We will focus on the integrity of the frontal eye fields (FEF), which receive substantial associational projections from DLPFC and which are believed to be a site of abnormalities causing eye movement dysfunctions in schizophrenia. Project is closely linked to Project-Lewis (which proposed postmortem histologic studies of DLPFC that parallel both our in vivo neuroimaging studies of that region as well as our histologic studies of FEF), Project-Levitt (which will conduct gene expression studies of FEF in postmortem tissue from schizophrenic patients), Project 6-Olson (which proposes unit recording studies of behaving monkeys performing the identical oculomotor tasks to be used in our clinical studies), and Project-Cohen (which proposes fMRI and cognitive studies of working memory disturbances in schizophrenia that parallel those proposed in this project).